dbSNP rs1455918852: REV1:p.Val1191Leu (chr2-99402317-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_016316.4(REV1):c.3571G>T(p.Val1191Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V1191M) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

REV1
NM_016316.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.53

Publications

1 publications found

Variant links:

Genes affected

REV1 (HGNC:14060): (REV1 DNA directed polymerase) This gene encodes a protein with similarity to the S. cerevisiae mutagenesis protein Rev1. The Rev1 proteins contain a BRCT domain, which is important in protein-protein interactions. A suggested role for the human Rev1-like protein is as a scaffold that recruits DNA polymerases involved in translesion synthesis (TLS) of damaged DNA. [provided by RefSeq, Mar 2016]

REV1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016316.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
REV1	NM_016316.4	MANE Select	c.3571G>T	p.Val1191Leu	missense	Exon 22 of 23	NP_057400.1	Q9UBZ9-1
REV1	NM_001321454.2		c.3679G>T	p.Val1227Leu	missense	Exon 23 of 24	NP_001308383.1
REV1	NM_001037872.3		c.3568G>T	p.Val1190Leu	missense	Exon 22 of 23	NP_001032961.1	Q9UBZ9-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
REV1	ENST00000258428.8	TSL:1 MANE Select	c.3571G>T	p.Val1191Leu	missense	Exon 22 of 23	ENSP00000258428.3	Q9UBZ9-1
REV1	ENST00000393445.7	TSL:1	c.3568G>T	p.Val1190Leu	missense	Exon 22 of 23	ENSP00000377091.3	Q9UBZ9-2
REV1	ENST00000879664.1		c.3679G>T	p.Val1227Leu	missense	Exon 23 of 24	ENSP00000549723.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1387090

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

690776

African (AFR)

AF:

0.00

AC:

AN:

31736

American (AMR)

AF:

0.00

AC:

AN:

40094

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25116

East Asian (EAS)

AF:

0.00

AC:

AN:

39282

South Asian (SAS)

AF:

0.00

AC:

AN:

80094

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52080

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5640

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1055352

Other (OTH)

AF:

0.00

AC:

AN:

57696

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.95

BayesDel_addAF

Uncertain

0.10

BayesDel_noAF

Benign

-0.090

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.043

Eigen

Pathogenic

0.86

Eigen_PC

Pathogenic

0.86

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.95

M_CAP

Benign

0.030

MetaRNN

Uncertain

0.67

MetaSVM

Benign

-0.89

MutationAssessor

Uncertain

2.6

PhyloP100

7.5

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-1.5

REVEL

Benign

0.26

Sift

Uncertain

0.019

Sift4G

Uncertain

0.055

Polyphen

1.0

Vest4

0.66

MutPred

0.35

Loss of methylation at K1192 (P = 0.0444)

MVP

0.54

MPC

2.5

ClinPred

0.94

GERP RS

6.1

Varity_R

0.80

gMVP

0.65

Mutation Taster

=49/51

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over